TDMS Study 96007-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:20:03 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #3/RATS CONTROL VS. GROUPS 6, 7, & 8 REASONS FOR REMOVAL: 25022 Accidently Killed 25018 Dosing Accident 25019 Moribund Sacrifice 25020 Natural Death 25021 Terminal Sacrifice REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE 001 0 NG/KG INCLUDE 006 300 NG/KG INCLUDE 007 550 NG/KG INCLUDE 008 1000 NG/KG NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:20:03 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TOXIC EQUIVALENCY FACTOR EVALUATION ( =============================================================== Female Rats ------------ Organ Morphology ----- ---------- Adrenal Cortex Angiectasis Atrophy Hypertrophy Vacuolization Cytoplasmic Adrenal Medulla Hyperplasia Blood Vessel: Aorta Mineralization Bone Marrow Hyperplasia Clitoral Gland Inflammation Clitoral Gland: Duct Cyst Eye: Cornea Inflammation Eye: Retina Atrophy Harderian Gland Inflammation Heart Cardiomyopathy Heart: Epicardium Inflammation Kidney Casts Protein Mineralization Nephropathy Kidney: Transitional Epithelium Hyperplasia Liver Cholangiofibrosis Clear Cell Focus Degeneration Cystic Eosinophilic Focus Fatty Change Diffuse Hepatocyte, Multinucleate Hyperplasia Inflammation Mixed Cell Focus Necrosis Pigmentation Toxic Hepatopathy Liver: Bile Duct Cyst Hyperplasia Liver: Hepatocyte Degeneration Hypertrophy Liver: Oval Cell Hyperplasia Liver: Portal Fibrosis Lung Infiltration Cellular Histiocyte Inflammation Chronic Inflammation Granulomatous Metaplasia Lung: Alveolar Epithelium Hyperplasia Metaplasia Bronchiolar Lymph Node, Mandibular Hyperplasia Lymph Node, Mesenteric Hyperplasia Lymphoid Lymph Node: Mediastinal Ectasia Hemorrhage Mammary Gland Cyst Hyperplasia NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TOXIC EQUIVALENCY FACTOR EVALUATION (PCB-126) DATE: 10/01/03 EXPERIMENT: 96007 TEST: 01 TIME: 12:20:03 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-75411 ROUTE: GAVAGE NTP C#: 96007D PATHOLOGIST: MISSING CAS: 57465-28-8 Inflammation Granulomatous Mesentery Inflammation Chronic Mesentery: Artery Inflammation Chronic Oral Mucosa: Gingival Hyperplasia Ovary Atrophy Pancreas Inflammation Chronic Pancreas: Acinus Atrophy Vacuolization Cytoplasmic Pancreas: Artery Inflammation Chronic Pancreas: Duct Dilatation Spleen Hyperplasia Lymphoid Pigmentation Spleen: Lymphoid Follicle Atrophy Stomach, Forestomach Hyperplasia Thymus Atrophy Thyroid Gland: C-Cell Hyperplasia Thyroid Gland: Follicular Cell Hypertrophy Tooth: Peridontal Tissue Inflammation Inflammation Chronic Ureter Metaplasia Uterus Inflammation Metaplasia Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 20/53 (38%) 8/52 (15%) 1/53 (2%) | |POLY-3 RATE (b) | 11/34.50 20/39.31 8/42.81 1/32.22 | |POLY-3 PERCENT (g) | 31.9% 50.9% 18.7% 3.1% | |TERMINAL (d) | 4/15 (27%) 12/16 (75%) 6/23 (26%) 0/7 (0%) | |FIRST INCIDENCE | 541 301 440 642 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.106 P=0.078N P=0.010N* | |POLY 3 | P<0.001N** P=0.069 P=0.140N P=0.002N** | |POLY 1.5 | P<0.001N** P=0.063 P=0.183N P=0.002N** | |POLY 6 | P<0.001N** P=0.061 P=0.109N P=0.004N** | |LOGISTIC REGRESSION| P<0.001N** P=0.095 P=0.179N P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.049 * P=0.306N P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 5/53 (9%) 19/52 (37%) 30/53 (57%) | |POLY-3 RATE (b) | 1/31.36 5/37.66 19/43.48 30/39.85 | |POLY-3 PERCENT (g) | 3.2% 13.3% 43.7% 75.3% | |TERMINAL (d) | 1/15 (7%) 2/16 (13%) 9/23 (39%) 6/7 (86%) | |FIRST INCIDENCE | 727 (T) 607 554 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.150 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.146 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.129 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.167 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.143 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.107 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/52 (21%) 14/53 (26%) 16/52 (31%) 10/53 (19%) | |POLY-3 RATE (b) | 11/34.41 14/40.61 16/43.78 10/35.87 | |POLY-3 PERCENT (g) | 32.0% 34.5% 36.5% 27.9% | |TERMINAL (d) | 4/15 (27%) 0/16 (0%) 8/23 (35%) 0/7 (0%) | |FIRST INCIDENCE | 496 531 535 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.447 P=0.548 P=0.528N P=0.515 | |POLY 3 | P=0.396N P=0.507 P=0.427 P=0.454N | |POLY 1.5 | P=0.384N P=0.440 P=0.336 P=0.448N | |POLY 6 | P=0.452N P=0.581 P=0.525 P=0.504N | |LOGISTIC REGRESSION| P=0.404N P=0.428 P=0.391 P=0.471N | |COCH-ARM / FISHERS | P=0.421N P=0.344 P=0.186 P=0.480N | |ORDER RESTRICTED | P=0.446N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 25/53 (47%) 31/52 (60%) 24/53 (45%) | |POLY-3 RATE (b) | 23/38.88 25/41.73 31/44.16 24/39.04 | |POLY-3 PERCENT (g) | 59.2% 59.9% 70.2% 61.5% | |TERMINAL (d) | 7/15 (47%) 10/16 (63%) 18/23 (78%) 4/7 (57%) | |FIRST INCIDENCE | 309 331 573 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.103 P=0.453N P=0.341N P=0.230 | |POLY 3 | P=0.370 P=0.566 P=0.191 P=0.509 | |POLY 1.5 | P=0.411 P=0.534 P=0.155 P=0.538 | |POLY 6 | P=0.279 P=0.572 P=0.219 P=0.419 | |LOGISTIC REGRESSION| P=0.467 P=0.565N P=0.363 P=0.567 | |COCH-ARM / FISHERS | P=0.425 P=0.458 P=0.085 P=0.535 | |ORDER RESTRICTED | P=0.401 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 34/52 (65%) 40/53 (75%) 41/52 (79%) 41/53 (77%) | |POLY-3 RATE (b) | 34/39.07 40/45.32 41/46.88 41/44.54 | |POLY-3 PERCENT (g) | 87.0% 88.3% 87.5% 92.0% | |TERMINAL (d) | 15/15 (100%) 14/16 (88%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 391 454 185 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.010 * P=0.558 P=0.095N P=0.013 * | |POLY 3 | P=0.251 P=0.575 P=0.625 P=0.299 | |POLY 1.5 | P=0.179 P=0.341 P=0.383 P=0.188 | |POLY 6 | P=0.323 P=0.470N P=0.465N P=0.534 | |LOGISTIC REGRESSION| P=0.158 P=0.446 P=0.538N P=0.176 | |COCH-ARM / FISHERS | P=0.106 P=0.179 P=0.095 P=0.127 | |ORDER RESTRICTED | P=0.315 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 1/53 (2%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.80 1/36.92 1/41.58 2/32.55 | |POLY-3 PERCENT (g) | 3.1% 2.7% 2.4% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 600 642 714 574 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.311 P=0.706N P=0.648N P=0.503 | |POLY 3 | P=0.354 P=0.727N P=0.698N P=0.508 | |POLY 1.5 | P=0.359 P=0.738N P=0.720N P=0.513 | |POLY 6 | P=0.341 P=0.717N P=0.672N P=0.484 | |LOGISTIC REGRESSION| P=0.353 P=0.750N P=0.731N P=0.509 | |COCH-ARM / FISHERS | P=0.354 P=0.748N P=0.752N P=0.507 | |ORDER RESTRICTED | P=0.381 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/52 (10%) 9/53 (17%) 4/52 (8%) 17/53 (32%) | |POLY-3 RATE (b) | 5/32.65 9/39.52 4/42.52 17/36.67 | |POLY-3 PERCENT (g) | 15.3% 22.8% 9.4% 46.4% | |TERMINAL (d) | 3/15 (20%) 2/16 (13%) 1/23 (4%) 3/7 (43%) | |FIRST INCIDENCE | 496 163 554 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.295 P=0.273N P<0.001 ** | |POLY 3 | P=0.003 ** P=0.308 P=0.338N P=0.004 ** | |POLY 1.5 | P=0.003 ** P=0.268 P=0.393N P=0.004 ** | |POLY 6 | P=0.002 ** P=0.358 P=0.281N P=0.003 ** | |LOGISTIC REGRESSION| P=0.003 ** P=0.224 P=0.422N P=0.004 ** | |COCH-ARM / FISHERS | P=0.003 ** P=0.206 P=0.500N P=0.004 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/53 (4%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 2/36.61 2/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 5.5% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 2/16 (13%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | --- 727 (T) 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.586 P=0.250 P=0.336 (e) | |POLY 3 | P=0.528N P=0.272 P=0.304 (e) | |POLY 1.5 | P=0.525N P=0.260 P=0.280 (e) | |POLY 6 | P=0.551N P=0.283 P=0.333 (e) | |LOGISTIC REGRESSION| (e) P=0.250 P=0.336 (e) | |COCH-ARM / FISHERS | P=0.537N P=0.252 P=0.248 (e) | |ORDER RESTRICTED | P=0.322N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 12/53 (23%) 6/52 (12%) 1/53 (2%) | |POLY-3 RATE (b) | 8/33.72 12/37.67 6/42.16 1/32.28 | |POLY-3 PERCENT (g) | 23.7% 31.9% 14.2% 3.1% | |TERMINAL (d) | 3/15 (20%) 5/16 (31%) 3/23 (13%) 0/7 (0%) | |FIRST INCIDENCE | 496 618 573 621 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017N* P=0.376 P=0.143N P=0.040N* | |POLY 3 | P=0.005N** P=0.305 P=0.224N P=0.015N* | |POLY 1.5 | P=0.004N** P=0.283 P=0.273N P=0.014N* | |POLY 6 | P=0.006N** P=0.320 P=0.180N P=0.023N* | |LOGISTIC REGRESSION| P=0.004N** P=0.362 P=0.248N P=0.016N* | |COCH-ARM / FISHERS | P=0.007N** P=0.243 P=0.387N P=0.014N* | |ORDER RESTRICTED | P=0.006N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Blood Vessel: Aorta | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/53 (0%) 2/53 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 3/32.76 0/36.61 2/42.83 0/31.91 | |POLY-3 PERCENT (g) | 9.2% 0.0% 4.7% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 583 --- 573 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.088N P=0.088N P=0.329N P=0.100N | |POLY 3 | P=0.117N P=0.098N P=0.380N P=0.121N | |POLY 1.5 | P=0.113N P=0.104N P=0.418N P=0.116N | |POLY 6 | P=0.124N P=0.095N P=0.345N P=0.142N | |LOGISTIC REGRESSION| P=0.111N P=0.118N P=0.512N P=0.119N | |COCH-ARM / FISHERS | P=0.111N P=0.121N P=0.500N P=0.121N | |ORDER RESTRICTED | P=0.038N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Bone | | Osteopetrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 0/53 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.38 2/38.22 0/42.13 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 5.2% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 40 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.414N P=0.258 (e) (e) | |POLY 3 | P=0.362N P=0.283 (e) (e) | |POLY 1.5 | P=0.381N P=0.267 (e) (e) | |POLY 6 | P=0.340N P=0.299 (e) (e) | |LOGISTIC REGRESSION| P=0.476N P=0.182 (e) (e) | |COCH-ARM / FISHERS | P=0.423N P=0.248 (e) (e) | |ORDER RESTRICTED | P=0.283N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Bone Marrow | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 47/53 (89%) 45/53 (85%) 46/53 (87%) 46/53 (87%) | |POLY-3 RATE (b) | 47/52.12 45/51.59 46/52.30 46/49.04 | |POLY-3 PERCENT (g) | 90.2% 87.2% 88.0% 93.8% | |TERMINAL (d) | 10/15 (67%) 12/16 (75%) 18/23 (78%) 7/7 (100%) | |FIRST INCIDENCE | 126 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.224 P=0.181N P=0.019N* P=0.265 | |POLY 3 | P=0.288 P=0.432N P=0.479N P=0.370 | |POLY 1.5 | P=0.423 P=0.399N P=0.476N P=0.545 | |POLY 6 | P=0.155 P=0.493N P=0.494N P=0.167 | |LOGISTIC REGRESSION| P=0.500N P=0.504N P=0.514 P=0.508N | |COCH-ARM / FISHERS | P=0.483N P=0.388N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.281 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 28/50 (56%) 30/53 (57%) 27/52 (52%) 22/51 (43%) | |POLY-3 RATE (b) | 28/40.18 30/44.65 27/47.18 22/42.43 | |POLY-3 PERCENT (g) | 69.7% 67.2% 57.2% 51.9% | |TERMINAL (d) | 9/14 (64%) 12/16 (75%) 11/23 (48%) 1/7 (14%) | |FIRST INCIDENCE | 222 301 320 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.329N P=0.385N P=0.043N* P=0.393N | |POLY 3 | P=0.032N* P=0.494N P=0.155N P=0.062N | |POLY 1.5 | P=0.034N* P=0.527N P=0.214N P=0.064N | |POLY 6 | P=0.041N* P=0.476N P=0.110N P=0.080N | |LOGISTIC REGRESSION| P=0.083N P=0.513N P=0.321N P=0.150N | |COCH-ARM / FISHERS | P=0.088N P=0.554 P=0.415N P=0.137N | |ORDER RESTRICTED | P=0.064N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Clitoral Gland: Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 29/50 (58%) 39/53 (74%) 42/52 (81%) 45/51 (88%) | |POLY-3 RATE (b) | 29/40.97 39/47.23 42/48.69 45/47.03 | |POLY-3 PERCENT (g) | 70.8% 82.6% 86.3% 95.7% | |TERMINAL (d) | 8/14 (57%) 11/16 (69%) 18/23 (78%) 6/7 (86%) | |FIRST INCIDENCE | 126 247 320 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.349 P=0.438N P=0.004 ** | |POLY 3 | P<0.001 ** P=0.126 P=0.049 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.090 P=0.025 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.177 P=0.094 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.100 P=0.033 * P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.072 P=0.011 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Esophagus: Muscularis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/53 (2%) 2/52 (4%) 0/52 (0%) | |POLY-3 RATE (b) | 2/30.96 1/36.86 2/41.73 0/31.53 | |POLY-3 PERCENT (g) | 6.5% 2.7% 4.8% 0.0% | |TERMINAL (d) | 1/14 (7%) 0/16 (0%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | 547 659 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.228N P=0.439N P=0.526N P=0.293N | |POLY 3 | P=0.200N P=0.439N P=0.582N P=0.231N | |POLY 1.5 | P=0.196N P=0.458N P=0.620N P=0.229N | |POLY 6 | P=0.212N P=0.421N P=0.540N P=0.247N | |LOGISTIC REGRESSION| P=0.179N P=0.455N P=0.574N P=0.231N | |COCH-ARM / FISHERS | P=0.199N P=0.493N P=0.691N P=0.248N | |ORDER RESTRICTED | P=0.150N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Eye: Cornea | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/53 (0%) 1/52 (2%) 2/52 (4%) | |POLY-3 RATE (b) | 0/30.21 0/36.61 1/41.54 2/31.74 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 6.3% | |TERMINAL (d) | 0/14 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 720 663 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.032 * (e) P=0.610 P=0.208 | |POLY 3 | P=0.065 (e) P=0.562 P=0.246 | |POLY 1.5 | P=0.068 (e) P=0.543 P=0.249 | |POLY 6 | P=0.060 (e) P=0.584 P=0.233 | |LOGISTIC REGRESSION| P=0.051 (e) P=0.619 P=0.231 | |COCH-ARM / FISHERS | P=0.069 (e) P=0.505 P=0.252 | |ORDER RESTRICTED | P=0.080 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Eye: Retina | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/53 (0%) 1/52 (2%) 4/52 (8%) | |POLY-3 RATE (b) | 0/30.21 0/36.61 1/41.53 4/32.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 12.3% | |TERMINAL (d) | 0/14 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- 722 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.602 P=0.031 * | |POLY 3 | P=0.006 ** (e) P=0.562 P=0.066 | |POLY 1.5 | P=0.006 ** (e) P=0.543 P=0.067 | |POLY 6 | P=0.005 ** (e) P=0.584 P=0.058 | |LOGISTIC REGRESSION| P=0.005 ** (e) P=0.622 P=0.066 | |COCH-ARM / FISHERS | P=0.006 ** (e) P=0.505 P=0.061 | |ORDER RESTRICTED | P=0.007 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/53 (6%) 3/52 (6%) 6/52 (12%) | |POLY-3 RATE (b) | 2/32.88 3/37.08 3/42.38 6/33.83 | |POLY-3 PERCENT (g) | 6.1% 8.1% 7.1% 17.7% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | 321 607 574 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.048 * P=0.581 P=0.632 P=0.110 | |POLY 3 | P=0.085 P=0.555 P=0.613 P=0.135 | |POLY 1.5 | P=0.085 P=0.536 P=0.573 P=0.139 | |POLY 6 | P=0.080 P=0.573 P=0.657 P=0.116 | |LOGISTIC REGRESSION| P=0.075 P=0.495 P=0.398 P=0.118 | |COCH-ARM / FISHERS | P=0.076 P=0.500 P=0.491 P=0.129 | |ORDER RESTRICTED | P=0.091 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/52 (17%) 24/53 (45%) 28/51 (55%) 32/51 (63%) | |POLY-3 RATE (b) | 9/35.59 24/41.08 28/45.07 32/39.46 | |POLY-3 PERCENT (g) | 25.3% 58.4% 62.1% 81.1% | |TERMINAL (d) | 2/15 (13%) 12/16 (75%) 12/23 (52%) 7/7 (100%) | |FIRST INCIDENCE | 201 331 554 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.012 * P=0.034 * P<0.001 ** | |POLY 3 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.002 ** P=0.002 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Heart: Epicardium | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 0/53 (0%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 2/32.82 0/36.61 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 6.1% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 126 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.080N P=0.217N P=0.204N P=0.228N | |POLY 3 | P=0.080N P=0.212N P=0.191N P=0.249N | |POLY 1.5 | P=0.084N P=0.221N P=0.208N P=0.244N | |POLY 6 | P=0.069N P=0.206N P=0.173N P=0.269N | |LOGISTIC REGRESSION| P=0.111N P=0.256N P=0.431N P=0.247N | |COCH-ARM / FISHERS | P=0.089N P=0.243N P=0.252N P=0.252N | |ORDER RESTRICTED | P=0.034N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Parasite Metazoan | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/53 (2%) 0/52 (0%) 1/53 (2%) | |POLY-3 RATE (b) | 2/30.87 1/37.22 0/41.53 1/31.91 | |POLY-3 PERCENT (g) | 6.5% 2.7% 0.0% 3.1% | |TERMINAL (d) | 2/15 (13%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | 727 (T) 531 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.405N P=0.465N P=0.149N P=0.723 | |POLY 3 | P=0.304N P=0.435N P=0.178N P=0.488N | |POLY 1.5 | P=0.312N P=0.455N P=0.196N P=0.482N | |POLY 6 | P=0.282N P=0.416N P=0.160N P=0.518N | |LOGISTIC REGRESSION| P=0.316N P=0.448N (e) P=0.723 | |COCH-ARM / FISHERS | P=0.324N P=0.493N P=0.248N P=0.493N | |ORDER RESTRICTED | P=0.194N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Erosion | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/53 (0%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.84 0/36.61 0/41.43 2/32.17 | |POLY-3 PERCENT (g) | 3.1% 0.0% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 583 --- --- 694 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.236 P=0.461N P=0.436N P=0.455 | |POLY 3 | P=0.272 P=0.472N P=0.448N P=0.504 | |POLY 1.5 | P=0.273 P=0.481N P=0.467N P=0.511 | |POLY 6 | P=0.274 P=0.465N P=0.429N P=0.475 | |LOGISTIC REGRESSION| P=0.266 P=0.499N P=0.534N P=0.499 | |COCH-ARM / FISHERS | P=0.272 P=0.495N P=0.505N P=0.507 | |ORDER RESTRICTED | P=0.122 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 0/53 (0%) 0/52 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 4/31.53 0/36.61 0/41.53 2/32.74 | |POLY-3 PERCENT (g) | 12.7% 0.0% 0.0% 6.1% | |TERMINAL (d) | 3/15 (20%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 688 --- --- 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.316N P=0.049N* P=0.020N* P=0.514N | |POLY 3 | P=0.261N P=0.042N* P=0.033N* P=0.316N | |POLY 1.5 | P=0.264N P=0.048N* P=0.041N* P=0.316N | |POLY 6 | P=0.243N P=0.037N* P=0.025N* P=0.338N | |LOGISTIC REGRESSION| P=0.257N P=0.035N* P=0.016N* P=0.369N | |COCH-ARM / FISHERS | P=0.268N P=0.059N P=0.061N P=0.339N | |ORDER RESTRICTED | P=0.024N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 0/53 (0%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 0/36.61 1/41.91 2/32.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 6.1% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 618 555 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.068 (e) P=0.596 P=0.281 | |POLY 3 | P=0.067 (e) P=0.557 P=0.246 | |POLY 1.5 | P=0.069 (e) P=0.536 P=0.247 | |POLY 6 | P=0.062 (e) P=0.579 P=0.234 | |LOGISTIC REGRESSION| P=0.069 (e) P=0.501 P=0.237 | |COCH-ARM / FISHERS | P=0.069 (e) P=0.495 P=0.248 | |ORDER RESTRICTED | P=0.080 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/53 (2%) 1/52 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.89 1/36.86 1/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 2.7% 2.4% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 574 659 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.155N P=0.446N P=0.366N P=0.302N | |POLY 3 | P=0.140N P=0.449N P=0.409N P=0.235N | |POLY 1.5 | P=0.140N P=0.467N P=0.441N P=0.231N | |POLY 6 | P=0.141N P=0.434N P=0.377N P=0.255N | |LOGISTIC REGRESSION| P=0.130N P=0.459N P=0.408N P=0.236N | |COCH-ARM / FISHERS | P=0.144N P=0.500N P=0.507N P=0.248N | |ORDER RESTRICTED | P=0.115N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 44/53 (83%) 39/52 (75%) 37/53 (70%) | |POLY-3 RATE (b) | 32/42.76 44/50.35 39/47.55 37/45.03 | |POLY-3 PERCENT (g) | 74.8% 87.4% 82.0% 82.2% | |TERMINAL (d) | 12/15 (80%) 14/16 (88%) 20/23 (87%) 6/7 (86%) | |FIRST INCIDENCE | 126 40 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.085 P=0.224 P=0.183N P=0.068 | |POLY 3 | P=0.349 P=0.080 P=0.267 P=0.258 | |POLY 1.5 | P=0.368 P=0.037 * P=0.186 P=0.258 | |POLY 6 | P=0.276 P=0.161 P=0.366 P=0.218 | |LOGISTIC REGRESSION| P=0.353 P=0.013 * P=0.250 P=0.234 | |COCH-ARM / FISHERS | P=0.310 P=0.008 ** P=0.082 P=0.208 | |ORDER RESTRICTED | P=0.182 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/53 (60%) 38/53 (72%) 42/52 (81%) 47/53 (89%) | |POLY-3 RATE (b) | 32/43.26 38/44.56 42/46.08 47/48.96 | |POLY-3 PERCENT (g) | 74.0% 85.3% 91.1% 96.0% | |TERMINAL (d) | 11/15 (73%) 14/16 (88%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 126 331 554 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.515 P=0.276N P=0.003 ** | |POLY 3 | P<0.001 ** P=0.116 P=0.014 * P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.096 P=0.011 * P<0.001 ** | |POLY 6 | P<0.001 ** P=0.163 P=0.025 * P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.239 P=0.095 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.153 P=0.018 * P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/53 (0%) 1/52 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 2/32.37 0/36.61 1/41.91 2/33.30 | |POLY-3 PERCENT (g) | 6.2% 0.0% 2.4% 6.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 574 --- 618 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.522 P=0.201N P=0.374N P=0.650N | |POLY 3 | P=0.488 P=0.210N P=0.411N P=0.686N | |POLY 1.5 | P=0.494 P=0.218N P=0.442N P=0.680N | |POLY 6 | P=0.477 P=0.204N P=0.381N P=0.681 | |LOGISTIC REGRESSION| P=0.474 P=0.239N P=0.534N P=0.681 | |COCH-ARM / FISHERS | P=0.493 P=0.248N P=0.507N P=0.691N | |ORDER RESTRICTED | P=0.365N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Pelvis | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/53 (6%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.53 3/38.48 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.2% 7.8% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 541 301 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.057N P=0.577 P=0.180N P=0.211N | |POLY 3 | P=0.058N P=0.577 P=0.187N P=0.240N | |POLY 1.5 | P=0.061N P=0.551 P=0.204N P=0.233N | |POLY 6 | P=0.054N P=0.598 P=0.172N P=0.263N | |LOGISTIC REGRESSION| P=0.088N P=0.454 P=0.284N P=0.241N | |COCH-ARM / FISHERS | P=0.072N P=0.500 P=0.252N P=0.248N | |ORDER RESTRICTED | P=0.107N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Kidney: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 8/53 (15%) 8/52 (15%) 11/53 (21%) | |POLY-3 RATE (b) | 4/32.45 8/38.99 8/42.50 11/35.55 | |POLY-3 PERCENT (g) | 12.3% 20.5% 18.8% 30.9% | |TERMINAL (d) | 2/15 (13%) 2/16 (13%) 4/23 (17%) 1/7 (14%) | |FIRST INCIDENCE | 554 301 618 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * P=0.272 P=0.443 P=0.023 * | |POLY 3 | P=0.053 P=0.273 P=0.331 P=0.054 | |POLY 1.5 | P=0.052 P=0.237 P=0.270 P=0.054 | |POLY 6 | P=0.048 * P=0.308 P=0.404 P=0.045 * | |LOGISTIC REGRESSION| P=0.043 * P=0.210 P=0.323 P=0.050 | |COCH-ARM / FISHERS | P=0.043 * P=0.179 P=0.170 P=0.046 * | |ORDER RESTRICTED | P=0.047 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/53 (2%) 2/51 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 3/31.69 1/36.76 2/41.43 2/32.00 | |POLY-3 PERCENT (g) | 9.5% 2.7% 4.8% 6.3% | |TERMINAL (d) | 2/15 (13%) 0/16 (0%) 2/23 (9%) 1/7 (14%) | |FIRST INCIDENCE | 644 688 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.557 P=0.256N P=0.312N P=0.594 | |POLY 3 | P=0.470N P=0.252N P=0.380N P=0.495N | |POLY 1.5 | P=0.467N P=0.270N P=0.425N P=0.487N | |POLY 6 | P=0.473N P=0.237N P=0.337N P=0.535N | |LOGISTIC REGRESSION| P=0.538N P=0.232N P=0.291N P=0.625N | |COCH-ARM / FISHERS | P=0.473N P=0.309N P=0.518N P=0.500N | |ORDER RESTRICTED | P=0.332N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 7/53 (13%) 4/53 (8%) 5/51 (10%) 5/53 (9%) | |POLY-3 RATE (b) | 7/32.51 4/36.97 5/41.49 5/32.77 | |POLY-3 PERCENT (g) | 21.5% 10.8% 12.1% 15.3% | |TERMINAL (d) | 3/15 (20%) 1/16 (6%) 4/23 (17%) 2/7 (29%) | |FIRST INCIDENCE | 541 658 714 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.521 P=0.182N P=0.129N P=0.545 | |POLY 3 | P=0.357N P=0.184N P=0.219N P=0.367N | |POLY 1.5 | P=0.354N P=0.209N P=0.274N P=0.357N | |POLY 6 | P=0.373N P=0.166N P=0.173N P=0.427N | |LOGISTIC REGRESSION| P=0.392N P=0.157N P=0.144N P=0.416N | |COCH-ARM / FISHERS | P=0.373N P=0.263N P=0.408N P=0.380N | |ORDER RESTRICTED | P=0.258N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Cholangiofibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/53 (6%) 13/51 (25%) 22/53 (42%) | |POLY-3 RATE (b) | 0/31.38 3/37.59 13/41.80 22/38.60 | |POLY-3 PERCENT (g) | 0.0% 8.0% 31.1% 57.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 10/23 (44%) 3/7 (43%) | |FIRST INCIDENCE | --- 607 651 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.182 P=0.002 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.153 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.140 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.169 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.133 P=0.002 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.121 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 0/53 (0%) 0/51 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.38 0/36.61 0/41.43 0/31.91 | |POLY-3 PERCENT (g) | 6.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/15 (13%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.087N P=0.222N P=0.149N P=0.416N | |POLY 3 | P=0.084N P=0.203N P=0.182N P=0.232N | |POLY 1.5 | P=0.087N P=0.215N P=0.201N P=0.229N | |POLY 6 | P=0.075N P=0.193N P=0.163N P=0.248N | |LOGISTIC REGRESSION| P=0.087N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.089N P=0.248N P=0.257N P=0.248N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Degeneration Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 1/53 (2%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.38 1/36.61 1/41.43 2/32.00 | |POLY-3 PERCENT (g) | 0.0% 2.7% 2.4% 6.3% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | --- 727 (T) 727 (T) 704 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.045 * P=0.513 P=0.585 P=0.105 | |POLY 3 | P=0.147 P=0.531 P=0.554 P=0.240 | |POLY 1.5 | P=0.150 P=0.520 P=0.534 P=0.243 | |POLY 6 | P=0.137 P=0.540 P=0.576 P=0.222 | |LOGISTIC REGRESSION| P=0.061 P=0.513 P=0.585 P=0.148 | |COCH-ARM / FISHERS | P=0.143 P=0.500 P=0.490 P=0.248 | |ORDER RESTRICTED | P=0.119 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/53 (21%) 17/53 (32%) 24/51 (47%) 17/53 (32%) | |POLY-3 RATE (b) | 11/34.24 17/39.64 24/47.33 17/41.05 | |POLY-3 PERCENT (g) | 32.1% 42.9% 50.7% 41.4% | |TERMINAL (d) | 5/15 (33%) 5/16 (31%) 7/23 (30%) 1/7 (14%) | |FIRST INCIDENCE | 405 531 440 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.041 * P=0.301 P=0.194 P=0.096 | |POLY 3 | P=0.278 P=0.233 P=0.073 P=0.272 | |POLY 1.5 | P=0.217 P=0.191 P=0.028 * P=0.226 | |POLY 6 | P=0.300 P=0.287 P=0.171 P=0.291 | |LOGISTIC REGRESSION| P=0.107 P=0.236 P=0.013 * P=0.135 | |COCH-ARM / FISHERS | P=0.099 P=0.135 P=0.004 ** P=0.135 | |ORDER RESTRICTED | P=0.168 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Diffuse | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 30/53 (57%) 45/51 (88%) 47/53 (89%) | |POLY-3 RATE (b) | 5/33.58 30/43.70 45/48.97 47/47.72 | |POLY-3 PERCENT (g) | 14.9% 68.7% 91.9% 98.5% | |TERMINAL (d) | 2/15 (13%) 10/16 (63%) 21/23 (91%) 7/7 (100%) | |FIRST INCIDENCE | 126 163 440 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 3/53 (6%) 2/51 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 2/32.02 3/36.91 2/42.21 0/31.91 | |POLY-3 PERCENT (g) | 6.3% 8.1% 4.7% 0.0% | |TERMINAL (d) | 1/15 (7%) 2/16 (13%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 519 645 440 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.178N P=0.554 P=0.576N P=0.302N | |POLY 3 | P=0.135N P=0.565 P=0.590N P=0.236N | |POLY 1.5 | P=0.135N P=0.543 P=0.630N P=0.232N | |POLY 6 | P=0.143N P=0.585 P=0.548N P=0.256N | |LOGISTIC REGRESSION| P=0.135N P=0.568 P=0.673 P=0.234N | |COCH-ARM / FISHERS | P=0.146N P=0.500 P=0.676 P=0.248N | |ORDER RESTRICTED | P=0.157N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hepatocyte, Multinucleate | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 19/53 (36%) 46/51 (90%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 19/39.58 46/47.56 49/50.73 | |POLY-3 PERCENT (g) | 0.0% 48.0% 96.7% 96.6% | |TERMINAL (d) | 0/15 (0%) 9/16 (56%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 331 440 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 3/53 (6%) 26/51 (51%) 39/53 (74%) | |POLY-3 RATE (b) | 0/31.38 3/36.86 26/43.63 39/42.89 | |POLY-3 PERCENT (g) | 0.0% 8.1% 59.6% 90.9% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 18/23 (78%) 7/7 (100%) | |FIRST INCIDENCE | --- 680 535 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.163 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.148 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.137 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.160 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.160 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.121 P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 36/53 (68%) 51/53 (96%) 51/51 (100%) 51/53 (96%) | |POLY-3 RATE (b) | 36/42.80 51/51.40 51/51.00 51/52.15 | |POLY-3 PERCENT (g) | 84.1% 99.2% 100.0% 97.8% | |TERMINAL (d) | 15/15 (100%) 16/16 (100%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 176 40 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.148 P=0.428N P=0.002 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P=0.004 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.009 ** P=0.006 ** P=0.004 ** P=0.019 * | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Mixed Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 21/53 (40%) 30/53 (57%) 29/51 (57%) 9/53 (17%) | |POLY-3 RATE (b) | 21/34.34 30/42.01 29/43.57 9/34.56 | |POLY-3 PERCENT (g) | 61.2% 71.4% 66.6% 26.0% | |TERMINAL (d) | 12/15 (80%) 15/16 (94%) 19/23 (83%) 3/7 (43%) | |FIRST INCIDENCE | 541 454 574 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.062N P=0.201 P=0.343N P=0.137N | |POLY 3 | P<0.001N** P=0.219 P=0.392 P<0.001N** | |POLY 1.5 | P<0.001N** P=0.130 P=0.230 P=0.002N** | |POLY 6 | P<0.001N** P=0.351 P=0.585 P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.198 P=0.480N P=0.005N** | |COCH-ARM / FISHERS | P=0.004N** P=0.060 P=0.059 P=0.008N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 11/53 (21%) 15/51 (29%) 17/53 (32%) | |POLY-3 RATE (b) | 4/34.03 11/39.49 15/44.94 17/38.49 | |POLY-3 PERCENT (g) | 11.8% 27.9% 33.4% 44.2% | |TERMINAL (d) | 0/15 (0%) 3/16 (19%) 6/23 (26%) 1/7 (14%) | |FIRST INCIDENCE | 176 403 185 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.112 P=0.064 P=0.004 ** | |POLY 3 | P=0.002 ** P=0.075 P=0.024 * P=0.002 ** | |POLY 1.5 | P=0.002 ** P=0.061 P=0.013 * P<0.001 ** | |POLY 6 | P=0.003 ** P=0.093 P=0.045 * P=0.002 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.047 * P=0.002 ** P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.046 * P=0.004 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 48/53 (91%) 51/51 (100%) 48/53 (91%) | |POLY-3 RATE (b) | 1/32.06 48/49.35 51/51.00 48/48.68 | |POLY-3 PERCENT (g) | 3.1% 97.3% 100.0% 98.6% | |TERMINAL (d) | 0/15 (0%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 496 247 185 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 23 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver | | Toxic Hepatopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 39/53 (74%) 51/51 (100%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 39/43.36 51/51.00 49/49.10 | |POLY-3 PERCENT (g) | 0.0% 90.0% 100.0% 99.8% | |TERMINAL (d) | 0/15 (0%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 541 185 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 3/53 (6%) 8/51 (16%) 12/53 (23%) | |POLY-3 RATE (b) | 3/31.38 3/36.99 8/41.43 12/35.10 | |POLY-3 PERCENT (g) | 9.6% 8.1% 19.3% 34.2% | |TERMINAL (d) | 3/15 (20%) 2/16 (13%) 8/23 (35%) 3/7 (43%) | |FIRST INCIDENCE | 727 (T) 618 727 (T) 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.618N P=0.272 P<0.001 ** | |POLY 3 | P=0.002 ** P=0.586N P=0.209 P=0.014 * | |POLY 1.5 | P=0.002 ** P=0.614N P=0.160 P=0.014 * | |POLY 6 | P<0.001 ** P=0.557N P=0.270 P=0.010 * | |LOGISTIC REGRESSION| P<0.001 ** P=0.556N P=0.272 P=0.012 * | |COCH-ARM / FISHERS | P=0.002 ** P=0.661N P=0.089 P=0.012 * | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 24 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/53 (8%) 1/53 (2%) 4/51 (8%) 5/53 (9%) | |POLY-3 RATE (b) | 4/32.23 1/36.86 4/42.20 5/33.91 | |POLY-3 PERCENT (g) | 12.4% 2.7% 9.5% 14.8% | |TERMINAL (d) | 3/15 (20%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 391 658 535 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.174 P=0.148N P=0.408N P=0.359 | |POLY 3 | P=0.274 P=0.137N P=0.489N P=0.533 | |POLY 1.5 | P=0.278 P=0.152N P=0.550N P=0.528 | |POLY 6 | P=0.262 P=0.124N P=0.423N P=0.516 | |LOGISTIC REGRESSION| P=0.276 P=0.149N P=0.564N P=0.512 | |COCH-ARM / FISHERS | P=0.271 P=0.181N P=0.620 P=0.500 | |ORDER RESTRICTED | P=0.254 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Bile Duct | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 14/53 (26%) 45/51 (88%) 45/53 (85%) | |POLY-3 RATE (b) | 3/32.67 14/39.77 45/47.42 45/45.98 | |POLY-3 PERCENT (g) | 9.2% 35.2% 94.9% 97.9% | |TERMINAL (d) | 1/15 (7%) 5/16 (31%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 496 328 535 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.008 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.006 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.011 * P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.006 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 25 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 1/53 (2%) 1/51 (2%) 7/53 (13%) | |POLY-3 RATE (b) | 3/33.04 1/36.68 1/41.62 7/34.41 | |POLY-3 PERCENT (g) | 9.1% 2.7% 2.4% 20.3% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 354 709 678 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.028 * P=0.256N P=0.191N P=0.129 | |POLY 3 | P=0.046 * P=0.267N P=0.228N P=0.165 | |POLY 1.5 | P=0.046 * P=0.279N P=0.256N P=0.169 | |POLY 6 | P=0.046 * P=0.257N P=0.201N P=0.145 | |LOGISTIC REGRESSION| P=0.046 * P=0.316N P=0.396N P=0.162 | |COCH-ARM / FISHERS | P=0.046 * P=0.309N P=0.324N P=0.160 | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Hepatocyte | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 42/53 (79%) 50/51 (98%) 49/53 (92%) | |POLY-3 RATE (b) | 0/31.38 42/46.52 50/50.61 49/49.44 | |POLY-3 PERCENT (g) | 0.0% 90.3% 98.8% 99.1% | |TERMINAL (d) | 0/15 (0%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 328 185 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 26 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Oval Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 10/53 (19%) 38/51 (75%) 40/53 (75%) | |POLY-3 RATE (b) | 0/31.38 10/37.11 38/44.37 40/43.32 | |POLY-3 PERCENT (g) | 0.0% 27.0% 85.6% 92.3% | |TERMINAL (d) | 0/15 (0%) 6/16 (38%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | --- 630 535 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Liver: Portal | | Fibrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 2/53 (4%) 1/51 (2%) 10/53 (19%) | |POLY-3 RATE (b) | 0/31.38 2/37.17 1/41.55 10/34.71 | |POLY-3 PERCENT (g) | 0.0% 5.4% 2.4% 28.8% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- 618 699 574 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.306 P=0.626 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.276 P=0.555 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.261 P=0.534 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.291 P=0.577 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.260 P=0.579 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.248 P=0.490 P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 27 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 41/53 (77%) 45/53 (85%) 49/51 (96%) 42/51 (82%) | |POLY-3 RATE (b) | 41/47.06 45/46.48 49/49.11 42/44.15 | |POLY-3 PERCENT (g) | 87.1% 96.8% 99.8% 95.1% | |TERMINAL (d) | 12/15 (80%) 15/16 (94%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 201 454 320 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.102 P=0.406N P=0.119N P=0.164 | |POLY 3 | P=0.041 * P=0.064 P=0.007 ** P=0.133 | |POLY 1.5 | P=0.053 P=0.070 P=0.004 ** P=0.156 | |POLY 6 | P=0.039 * P=0.100 P=0.019 * P=0.128 | |LOGISTIC REGRESSION| P=0.382 P=0.410 P=0.037 * P=0.445 | |COCH-ARM / FISHERS | P=0.224 P=0.229 P=0.005 ** P=0.349 | |ORDER RESTRICTED | P=0.006 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/53 (9%) 1/53 (2%) 0/51 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 5/32.66 1/37.61 0/41.13 2/31.84 | |POLY-3 PERCENT (g) | 15.3% 2.7% 0.0% 6.3% | |TERMINAL (d) | 2/15 (13%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 309 40 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.146N P=0.086N P=0.011N* P=0.375N | |POLY 3 | P=0.119N P=0.069N P=0.015N* P=0.220N | |POLY 1.5 | P=0.125N P=0.079N P=0.020N* P=0.219N | |POLY 6 | P=0.105N P=0.062N P=0.011N* P=0.244N | |LOGISTIC REGRESSION| P=0.152N P=0.121N P=0.027N* P=0.225N | |COCH-ARM / FISHERS | P=0.133N P=0.103N P=0.031N* P=0.235N | |ORDER RESTRICTED | P=0.022N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 28 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/53 (6%) 0/53 (0%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 3/32.04 0/36.61 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 9.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 611 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026N* P=0.097N P=0.057N P=0.179N | |POLY 3 | P=0.030N* P=0.095N P=0.080N P=0.122N | |POLY 1.5 | P=0.032N* P=0.102N P=0.094N P=0.120N | |POLY 6 | P=0.026N* P=0.090N P=0.069N P=0.137N | |LOGISTIC REGRESSION| P=0.027N* P=0.095N P=0.082N P=0.127N | |COCH-ARM / FISHERS | P=0.034N* P=0.121N P=0.129N P=0.129N | |ORDER RESTRICTED | P=0.009N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/53 (2%) 3/53 (6%) 9/51 (18%) 4/51 (8%) | |POLY-3 RATE (b) | 1/31.53 3/37.05 9/42.85 4/31.72 | |POLY-3 PERCENT (g) | 3.2% 8.1% 21.0% 12.6% | |TERMINAL (d) | 0/15 (0%) 2/16 (13%) 2/23 (9%) 2/7 (29%) | |FIRST INCIDENCE | 688 599 573 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039 * P=0.365 P=0.066 P=0.092 | |POLY 3 | P=0.093 P=0.364 P=0.030 * P=0.175 | |POLY 1.5 | P=0.099 P=0.343 P=0.018 * P=0.177 | |POLY 6 | P=0.072 P=0.384 P=0.051 P=0.157 | |LOGISTIC REGRESSION| P=0.090 P=0.372 P=0.021 * P=0.153 | |COCH-ARM / FISHERS | P=0.099 P=0.309 P=0.007 ** P=0.170 | |ORDER RESTRICTED | P=0.069 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 29 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/53 (23%) 2/53 (4%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 12/32.58 2/37.28 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 36.8% 5.4% 0.0% 0.0% | |TERMINAL (d) | 7/15 (47%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 600 607 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.002N** P<0.001N** P=0.005N** | |POLY 3 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 1.5 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |POLY 6 | P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P<0.001N** P<0.001N** P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.004N** P<0.001N** P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Metaplasia Bronchiolar | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/53 (0%) 39/53 (74%) 47/51 (92%) 40/51 (78%) | |POLY-3 RATE (b) | 0/31.38 39/44.76 47/48.24 40/43.59 | |POLY-3 PERCENT (g) | 0.0% 87.1% 97.4% 91.8% | |TERMINAL (d) | 0/15 (0%) 15/16 (94%) 23/23 (100%) 6/7 (86%) | |FIRST INCIDENCE | --- 454 320 394 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 30 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lung: Serosa | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 1/53 (2%) 0/51 (0%) 0/51 (0%) | |POLY-3 RATE (b) | 2/32.84 1/37.59 0/41.13 0/30.95 | |POLY-3 PERCENT (g) | 6.1% 2.7% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 126 163 --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.081N P=0.476N P=0.204N P=0.228N | |POLY 3 | P=0.080N P=0.453N P=0.191N P=0.249N | |POLY 1.5 | P=0.084N P=0.468N P=0.209N P=0.244N | |POLY 6 | P=0.071N P=0.441N P=0.174N P=0.268N | |LOGISTIC REGRESSION| P=0.125N P=0.584N P=0.449N P=0.270N | |COCH-ARM / FISHERS | P=0.090N P=0.500N P=0.257N P=0.257N | |ORDER RESTRICTED | P=0.081N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 4/52 (8%) 4/51 (8%) 3/51 (6%) | |POLY-3 RATE (b) | 1/31.47 4/35.81 4/41.14 3/30.95 | |POLY-3 PERCENT (g) | 3.2% 11.2% 9.7% 9.7% | |TERMINAL (d) | 0/15 (0%) 3/16 (19%) 3/23 (13%) 3/7 (43%) | |FIRST INCIDENCE | 660 722 722 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.093 P=0.215 P=0.339 P=0.115 | |POLY 3 | P=0.300 P=0.217 P=0.270 P=0.296 | |POLY 1.5 | P=0.309 P=0.204 P=0.235 P=0.304 | |POLY 6 | P=0.266 P=0.228 P=0.311 P=0.265 | |LOGISTIC REGRESSION| P=0.146 P=0.243 P=0.345 P=0.188 | |COCH-ARM / FISHERS | P=0.296 P=0.181 P=0.175 P=0.301 | |ORDER RESTRICTED | P=0.277 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 31 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/52 (35%) 29/52 (56%) 11/51 (22%) 15/51 (29%) | |POLY-3 RATE (b) | 18/36.75 29/42.17 11/42.99 15/36.60 | |POLY-3 PERCENT (g) | 49.0% 68.8% 25.6% 41.0% | |TERMINAL (d) | 8/15 (53%) 12/16 (75%) 5/23 (22%) 1/7 (14%) | |FIRST INCIDENCE | 222 163 320 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.236N P=0.127 P=0.009N** P=0.552 | |POLY 3 | P=0.032N* P=0.046 * P=0.023N* P=0.318N | |POLY 1.5 | P=0.041N* P=0.035 * P=0.038N* P=0.327N | |POLY 6 | P=0.027N* P=0.065 P=0.013N* P=0.329N | |LOGISTIC REGRESSION| P=0.064N P=0.043 * P=0.059N P=0.338N | |COCH-ARM / FISHERS | P=0.078N P=0.024 * P=0.105N P=0.362N | |ORDER RESTRICTED | P=0.010N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/52 (4%) 0/51 (0%) 1/51 (2%) | |POLY-3 RATE (b) | 0/31.21 2/36.75 0/41.11 1/30.95 | |POLY-3 PERCENT (g) | 0.0% 5.4% 0.0% 3.2% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- 247 --- 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.423 P=0.254 (e) P=0.348 | |POLY 3 | P=0.535 P=0.274 (e) P=0.498 | |POLY 1.5 | P=0.528 P=0.262 (e) P=0.501 | |POLY 6 | P=0.533 P=0.287 (e) P=0.484 | |LOGISTIC REGRESSION| P=0.495 P=0.211 (e) P=0.348 | |COCH-ARM / FISHERS | P=0.502 P=0.248 (e) P=0.495 | |ORDER RESTRICTED | P=0.322 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 32 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 1/53 (2%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 2/31.83 1/36.68 0/41.43 2/33.24 | |POLY-3 PERCENT (g) | 6.3% 2.7% 0.0% 6.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 618 709 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.584 P=0.411N P=0.137N P=0.653 | |POLY 3 | P=0.576N P=0.450N P=0.184N P=0.681N | |POLY 1.5 | P=0.585N P=0.466N P=0.202N P=0.677N | |POLY 6 | P=0.556N P=0.438N P=0.167N P=0.692 | |LOGISTIC REGRESSION| P=0.600N P=0.441N P=0.192N P=0.688N | |COCH-ARM / FISHERS | P=0.600N P=0.493N P=0.252N P=0.684N | |ORDER RESTRICTED | P=0.358N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 1/53 (2%) 1/51 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 3/33.26 1/36.61 1/41.46 1/32.33 | |POLY-3 PERCENT (g) | 9.0% 2.7% 2.4% 3.1% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 222 727 (T) 720 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.218N P=0.259N P=0.199N P=0.269N | |POLY 3 | P=0.205N P=0.270N P=0.231N P=0.313N | |POLY 1.5 | P=0.208N P=0.280N P=0.257N P=0.302N | |POLY 6 | P=0.198N P=0.263N P=0.206N P=0.348N | |LOGISTIC REGRESSION| P=0.220N P=0.322N P=0.433N P=0.309N | |COCH-ARM / FISHERS | P=0.212N P=0.302N P=0.316N P=0.302N | |ORDER RESTRICTED | P=0.172N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 33 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/53 (0%) 0/51 (0%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 0/36.61 0/41.43 2/32.53 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.028 * (e) (e) P=0.172 | |POLY 3 | P=0.050 (e) (e) P=0.244 | |POLY 1.5 | P=0.050 (e) (e) P=0.246 | |POLY 6 | P=0.050 (e) (e) P=0.228 | |LOGISTIC REGRESSION| P=0.049 * (e) (e) P=0.243 | |COCH-ARM / FISHERS | P=0.051 (e) (e) P=0.252 | |ORDER RESTRICTED | P=0.032 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Lumbar | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/4 (0%) 2/7 (29%) 0/12 (0%) | |POLY-3 RATE (b) | 0/0.63 0/2.47 2/6.05 0/7.43 | |POLY-3 PERCENT (g) | 0.0% 0.0% 33.1% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- 651 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.495 (e) P=0.391 (e) | |POLY 3 | P=0.369N (e) P=0.710 (e) | |POLY 1.5 | P=0.366N (e) P=0.673 (e) | |POLY 6 | P=0.413N (e) P=0.747 (e) | |LOGISTIC REGRESSION| P=0.454N (e) P=0.800 (e) | |COCH-ARM / FISHERS | P=0.466N (e) P=0.583 (e) | |ORDER RESTRICTED | P=0.642N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 34 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/4 (0%) 0/7 (0%) 5/12 (42%) | |POLY-3 RATE (b) | 0/0.63 0/2.47 0/5.66 5/9.34 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 53.5% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 1/1 (100%) | |FIRST INCIDENCE | --- --- --- 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.066 | |POLY 3 | P=0.013 * (e) (e) P=0.630 | |POLY 1.5 | P=0.016 * (e) (e) P=0.567 | |POLY 6 | P=0.010 * (e) (e) P=0.714 | |LOGISTIC REGRESSION| P=0.019 * (e) (e) P=0.494 | |COCH-ARM / FISHERS | P=0.022 * (e) (e) P=0.396 | |ORDER RESTRICTED | P=0.544 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 1/4 (25%) 0/7 (0%) 6/12 (50%) | |POLY-3 RATE (b) | 0/0.63 1/2.86 0/5.66 6/10.24 | |POLY-3 PERCENT (g) | 0.0% 35.0% 0.0% 58.6% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- 618 --- 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.543 (e) P=0.019 * | |POLY 3 | P=0.053 P=0.744 (e) P=0.604 | |POLY 1.5 | P=0.051 P=0.715 (e) P=0.529 | |POLY 6 | P=0.052 P=0.778 (e) P=0.695 | |LOGISTIC REGRESSION| P=0.026 * P=0.765 (e) P=0.243 | |COCH-ARM / FISHERS | P=0.043 * P=0.667 (e) P=0.308 | |ORDER RESTRICTED | P=0.550 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 35 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/2 (0%) 0/4 (0%) 0/7 (0%) 2/12 (17%) | |POLY-3 RATE (b) | 0/0.63 0/2.47 0/5.66 2/8.62 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 23.2% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/2 (0%) 0/1 (0%) | |FIRST INCIDENCE | --- --- --- 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.056 (e) (e) P=0.285 | |POLY 3 | P=0.216 (e) (e) P=0.782 | |POLY 1.5 | P=0.217 (e) (e) P=0.757 | |POLY 6 | P=0.207 (e) (e) P=0.812 | |LOGISTIC REGRESSION| P=0.108 (e) (e) P=0.590 | |COCH-ARM / FISHERS | P=0.185 (e) (e) P=0.725 | |ORDER RESTRICTED | P=0.640 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/52 (15%) 5/53 (9%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 8/33.57 5/37.22 1/41.88 1/32.31 | |POLY-3 PERCENT (g) | 23.8% 13.4% 2.4% 3.1% | |TERMINAL (d) | 3/15 (20%) 4/16 (25%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 405 531 628 611 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.004N** P=0.205N P=0.004N** P=0.051N | |POLY 3 | P=0.002N** P=0.203N P=0.005N** P=0.015N* | |POLY 1.5 | P=0.002N** P=0.223N P=0.008N** P=0.014N* | |POLY 6 | P=0.002N** P=0.190N P=0.003N** P=0.021N* | |LOGISTIC REGRESSION| P=0.003N** P=0.200N P=0.011N* P=0.016N* | |COCH-ARM / FISHERS | P=0.004N** P=0.265N P=0.016N* P=0.014N* | |ORDER RESTRICTED | P=0.003N** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 36 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 32/52 (62%) 21/53 (40%) 23/52 (44%) 9/53 (17%) | |POLY-3 RATE (b) | 32/43.06 21/40.32 23/45.33 9/34.10 | |POLY-3 PERCENT (g) | 74.3% 52.1% 50.7% 26.4% | |TERMINAL (d) | 11/15 (73%) 7/16 (44%) 10/23 (44%) 4/7 (57%) | |FIRST INCIDENCE | 126 531 185 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001N** P=0.016N* P=0.002N** P=0.002N** | |POLY 3 | P<0.001N** P=0.020N* P=0.013N* P<0.001N** | |POLY 1.5 | P<0.001N** P=0.022N* P=0.023N* P<0.001N** | |POLY 6 | P<0.001N** P=0.019N* P=0.007N** P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.011N* P=0.045N* P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.020N* P=0.058N P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 2/53 (4%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 1/31.36 2/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 3.2% 5.5% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 2/16 (13%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 727 (T) 727 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.232N P=0.523 P=0.415N P=0.652N | |POLY 3 | P=0.158N P=0.554 P=0.445N P=0.497N | |POLY 1.5 | P=0.167N P=0.536 P=0.464N P=0.493N | |POLY 6 | P=0.146N P=0.571 P=0.424N P=0.512N | |LOGISTIC REGRESSION| P=0.232N P=0.523 (e) (e) | |COCH-ARM / FISHERS | P=0.184N P=0.507 P=0.500N P=0.495N | |ORDER RESTRICTED | P=0.193N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 37 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mammary Gland | | Inflammation Granulomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/52 (4%) 0/53 (0%) 0/52 (0%) 0/53 (0%) | |POLY-3 RATE (b) | 2/31.43 0/36.61 0/41.53 0/31.91 | |POLY-3 PERCENT (g) | 6.4% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 709 --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.082N P=0.203N P=0.137N P=0.410N | |POLY 3 | P=0.081N P=0.204N P=0.181N P=0.232N | |POLY 1.5 | P=0.084N P=0.214N P=0.199N P=0.229N | |POLY 6 | P=0.072N P=0.194N P=0.163N P=0.249N | |LOGISTIC REGRESSION| P=0.071N P=0.186N P=0.130N P=0.330N | |COCH-ARM / FISHERS | P=0.086N P=0.243N P=0.248N P=0.243N | |ORDER RESTRICTED | P=0.028N* (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mesentery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/7 (0%) 0/13 (0%) 3/11 (27%) | |POLY-3 RATE (b) | 1/1.00 0/6.22 0/10.00 3/8.85 | |POLY-3 PERCENT (g) | 100.0% 0.0% 0.0% 33.9% | |TERMINAL (d) | 0/0 (0%) 0/4 (0%) 0/3 (0%) 1/2 (50%) | |FIRST INCIDENCE | 391 --- --- 562 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.113 P=0.473N P=0.440N P=0.544 | |POLY 3 | P=0.345 P<0.001N** P<0.001N** P=0.408N | |POLY 1.5 | P=0.328 P<0.001N** P<0.001N** P=0.379N | |POLY 6 | P=0.403 P<0.001N** P<0.001N** P=0.472N | |LOGISTIC REGRESSION| P=0.270 (e) P=0.168N P=0.983N | |COCH-ARM / FISHERS | P=0.328 P=0.125N P=0.071N P=0.333N | |ORDER RESTRICTED | P=0.249N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 38 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Mesentery: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/1 (0%) 6/7 (86%) 10/13 (77%) 7/11 (64%) | |POLY-3 RATE (b) | 0/0.16 6/6.85 10/11.50 7/9.70 | |POLY-3 PERCENT (g) | 0.0% 87.6% 87.0% 72.2% | |TERMINAL (d) | 0/0 (0%) 4/4 (100%) 3/3 (100%) 1/2 (50%) | |FIRST INCIDENCE | --- 618 573 607 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.008 ** P=0.310 P=0.050 P=0.014 * | |POLY 3 | P=0.289N P=0.873 P=0.899 P=0.840 | |POLY 1.5 | P=0.288N P=0.699 P=0.708 P=0.711 | |POLY 6 | P=0.362N P=0.955 P=0.983 P=0.922 | |LOGISTIC REGRESSION| P=0.417N (e) P=0.978 P=0.991 | |COCH-ARM / FISHERS | P=0.484N P=0.250 P=0.286 P=0.417 | |ORDER RESTRICTED | P=0.682 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Respiratory Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/52 (4%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 2/32.23 2/36.06 2/42.16 1/32.29 | |POLY-3 PERCENT (g) | 6.2% 5.6% 4.7% 3.1% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 391 607 720 618 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.453N P=0.648N P=0.550N P=0.577N | |POLY 3 | P=0.360N P=0.654N P=0.593N P=0.499N | |POLY 1.5 | P=0.358N P=0.671N P=0.628N P=0.493N | |POLY 6 | P=0.369N P=0.639N P=0.555N P=0.526N | |LOGISTIC REGRESSION| P=0.358N P=0.689N P=0.658N P=0.499N | |COCH-ARM / FISHERS | P=0.370N P=0.684 P=0.691N P=0.500N | |ORDER RESTRICTED | P=0.461N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 39 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Nose: Turbinate | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/53 (4%) 2/52 (4%) 0/53 (0%) 4/53 (8%) | |POLY-3 RATE (b) | 2/31.81 2/36.29 0/42.13 4/32.97 | |POLY-3 PERCENT (g) | 6.3% 5.5% 0.0% 12.1% | |TERMINAL (d) | 1/15 (7%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 603 607 --- 611 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.201 P=0.608N P=0.155N P=0.251 | |POLY 3 | P=0.275 P=0.647N P=0.181N P=0.350 | |POLY 1.5 | P=0.271 P=0.666N P=0.198N P=0.354 | |POLY 6 | P=0.280 P=0.629N P=0.164N P=0.323 | |LOGISTIC REGRESSION| P=0.256 P=0.665N P=0.184N P=0.333 | |COCH-ARM / FISHERS | P=0.256 P=0.684 P=0.248N P=0.339 | |ORDER RESTRICTED | P=0.116 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oral Mucosa: Gingival | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/2 (0%) 4/6 (67%) 3/11 (27%) | |POLY-3 RATE (b) | 1/1.00 0/1.61 4/5.29 3/8.09 | |POLY-3 PERCENT (g) | 100.0% 0.0% 75.6% 37.1% | |TERMINAL (d) | 1/1 (100%) 0/1 (0%) 3/3 (100%) 1/1 (100%) | |FIRST INCIDENCE | 727 (T) --- 651 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.043 * P=0.500N P=0.627 P=0.247 | |POLY 3 | P=0.249N P=0.085N P=0.783N P=0.438N | |POLY 1.5 | P=0.217N P<0.001N** P=0.741N P=0.392N | |POLY 6 | P=0.375N P=0.303N P=0.822N P=0.546N | |LOGISTIC REGRESSION| P=0.471N (e) P=0.872N P=0.529N | |COCH-ARM / FISHERS | P=0.214N P=0.333N P=0.714N P=0.333N | |ORDER RESTRICTED | P=0.396N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 40 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 45/52 (87%) 47/52 (90%) 46/52 (88%) 33/53 (62%) | |POLY-3 RATE (b) | 45/46.65 47/49.76 46/50.55 33/43.43 | |POLY-3 PERCENT (g) | 96.5% 94.5% 91.0% 76.0% | |TERMINAL (d) | 14/15 (93%) 15/16 (94%) 22/23 (96%) 5/7 (71%) | |FIRST INCIDENCE | 126 163 320 243 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.254N P=0.310N P=0.016N* P=0.336N | |POLY 3 | P<0.001N** P=0.508N P=0.232N P<0.001N** | |POLY 1.5 | P<0.001N** P=0.619N P=0.360N P<0.001N** | |POLY 6 | P<0.001N** P=0.539N P=0.195N P=0.005N** | |LOGISTIC REGRESSION| P<0.001N** P=0.492 P=0.388N P=0.002N** | |COCH-ARM / FISHERS | P<0.001N** P=0.380 P=0.500 P=0.004N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 16/52 (31%) 18/52 (35%) 11/53 (21%) | |POLY-3 RATE (b) | 12/33.36 16/40.40 18/44.23 11/35.26 | |POLY-3 PERCENT (g) | 36.0% 39.6% 40.7% 31.2% | |TERMINAL (d) | 7/15 (47%) 6/16 (38%) 9/23 (39%) 1/7 (14%) | |FIRST INCIDENCE | 547 331 498 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.366 P=0.419 P=0.552N P=0.380 | |POLY 3 | P=0.361N P=0.468 P=0.425 P=0.433N | |POLY 1.5 | P=0.361N P=0.378 P=0.304 P=0.440N | |POLY 6 | P=0.397N P=0.567 P=0.569 P=0.465N | |LOGISTIC REGRESSION| P=0.382N P=0.348 P=0.415 P=0.492N | |COCH-ARM / FISHERS | P=0.402N P=0.254 P=0.140 P=0.479N | |ORDER RESTRICTED | P=0.408N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 41 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ovary | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/52 (0%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 0/35.84 2/41.53 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 2/23 (9%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.431 (e) P=0.336 (e) | |POLY 3 | P=0.494 (e) P=0.304 (e) | |POLY 1.5 | P=0.523 (e) P=0.280 (e) | |POLY 6 | P=0.422 (e) P=0.333 (e) | |LOGISTIC REGRESSION| (e) (e) P=0.336 (e) | |COCH-ARM / FISHERS | P=0.542 (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.303 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Oviduct | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/1 (100%) 0/1 (0%) 2/3 (67%) 1/1 (100%) | |POLY-3 RATE (b) | 1/1.00 0/0.98 2/2.72 1/1.00 | |POLY-3 PERCENT (g) | 100.0% 0.0% 73.6% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 2/2 (100%) 1/1 (100%) | |FIRST INCIDENCE | 709 --- 727 (T) 727 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.282N P=0.477N P=0.411N (e) | |POLY 3 | P=0.603 P=1.000N P=0.786N (e) | |POLY 1.5 | P=0.593 P=1.000N P=0.737N (e) | |POLY 6 | P=0.627 P=1.000N P=0.885N (e) | |LOGISTIC REGRESSION| P=0.714 (e) P=0.411N (e) | |COCH-ARM / FISHERS | P=0.604 P=0.500N P=0.750N (e) | |ORDER RESTRICTED | P=0.426 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 42 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 4/53 (8%) 6/52 (12%) 13/51 (25%) | |POLY-3 RATE (b) | 5/32.80 4/37.40 6/43.08 13/35.71 | |POLY-3 PERCENT (g) | 15.2% 10.7% 13.9% 36.4% | |TERMINAL (d) | 3/15 (20%) 0/16 (0%) 1/23 (4%) 2/7 (29%) | |FIRST INCIDENCE | 391 618 573 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.405N P=0.478N P=0.019 * | |POLY 3 | P=0.008 ** P=0.416N P=0.566N P=0.037 * | |POLY 1.5 | P=0.007 ** P=0.442N P=0.623 P=0.034 * | |POLY 6 | P=0.008 ** P=0.387N P=0.486N P=0.040 * | |LOGISTIC REGRESSION| P=0.007 ** P=0.435N P=0.563 P=0.034 * | |COCH-ARM / FISHERS | P=0.008 ** P=0.475N P=0.514 P=0.034 * | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/51 (10%) 2/53 (4%) 11/52 (21%) 18/51 (35%) | |POLY-3 RATE (b) | 5/31.43 2/37.14 11/43.58 18/37.39 | |POLY-3 PERCENT (g) | 15.9% 5.4% 25.2% 48.1% | |TERMINAL (d) | 4/15 (27%) 0/16 (0%) 2/23 (9%) 2/7 (29%) | |FIRST INCIDENCE | 705 618 573 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.164N P=0.382 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.149N P=0.248 P=0.003 ** | |POLY 1.5 | P<0.001 ** P=0.170N P=0.175 P=0.002 ** | |POLY 6 | P<0.001 ** P=0.128N P=0.359 P=0.005 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.132N P=0.244 P=0.002 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.203N P=0.093 P=0.002 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 43 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Acinus | | Vacuolization Cytoplasmic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 9/53 (17%) 20/52 (38%) 23/51 (45%) | |POLY-3 RATE (b) | 0/31.35 9/37.20 20/42.74 23/36.28 | |POLY-3 PERCENT (g) | 0.0% 24.2% 46.8% 63.4% | |TERMINAL (d) | 0/15 (0%) 6/16 (38%) 14/23 (61%) 6/7 (86%) | |FIRST INCIDENCE | --- 607 618 525 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.003 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.004 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.005 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.002 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 8/53 (15%) 15/52 (29%) 11/51 (22%) | |POLY-3 RATE (b) | 0/31.35 8/37.31 15/42.61 11/35.04 | |POLY-3 PERCENT (g) | 0.0% 21.4% 35.2% 31.4% | |TERMINAL (d) | 0/15 (0%) 5/16 (31%) 8/23 (35%) 2/7 (29%) | |FIRST INCIDENCE | --- 618 588 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.009 ** P=0.002 ** P<0.001 ** | |POLY 3 | P=0.002 ** P=0.007 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P=0.002 ** P=0.006 ** P<0.001 ** P<0.001 ** | |POLY 6 | P=0.002 ** P=0.008 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.010 * P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P=0.002 ** P=0.003 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 44 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Duct | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/53 (0%) 0/52 (0%) 2/51 (4%) | |POLY-3 RATE (b) | 0/31.35 0/36.61 0/41.53 2/31.51 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.4% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.035 * (e) (e) P=0.230 | |POLY 3 | P=0.047 * (e) (e) P=0.236 | |POLY 1.5 | P=0.048 * (e) (e) P=0.239 | |POLY 6 | P=0.047 * (e) (e) P=0.225 | |LOGISTIC REGRESSION| P=0.044 * (e) (e) P=0.233 | |COCH-ARM / FISHERS | P=0.048 * (e) (e) P=0.248 | |ORDER RESTRICTED | P=0.029 * (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pancreas: Duct | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/53 (0%) 2/52 (4%) 0/51 (0%) | |POLY-3 RATE (b) | 0/31.35 0/36.61 2/41.71 0/30.95 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 678 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.477 (e) P=0.362 (e) | |POLY 3 | P=0.484 (e) P=0.305 (e) | |POLY 1.5 | P=0.512 (e) P=0.281 (e) | |POLY 6 | P=0.419 (e) P=0.335 (e) | |LOGISTIC REGRESSION| P=0.517 (e) P=0.329 (e) | |COCH-ARM / FISHERS | P=0.537 (e) P=0.252 (e) | |ORDER RESTRICTED | P=0.305 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 45 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 14/51 (27%) 16/53 (30%) 19/53 (36%) 9/53 (17%) | |POLY-3 RATE (b) | 14/33.32 16/38.31 19/44.06 9/33.36 | |POLY-3 PERCENT (g) | 42.0% 41.8% 43.1% 27.0% | |TERMINAL (d) | 7/15 (47%) 8/16 (50%) 12/23 (52%) 3/7 (43%) | |FIRST INCIDENCE | 546 607 588 588 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.498N P=0.557N P=0.410N P=0.573N | |POLY 3 | P=0.130N P=0.590N P=0.554 P=0.139N | |POLY 1.5 | P=0.116N P=0.561 P=0.444 P=0.127N | |POLY 6 | P=0.185N P=0.569N P=0.531N P=0.202N | |LOGISTIC REGRESSION| P=0.141N P=0.500N P=0.536N P=0.176N | |COCH-ARM / FISHERS | P=0.135N P=0.464 P=0.239 P=0.147N | |ORDER RESTRICTED | P=0.157N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 0/53 (0%) 2/53 (4%) 1/53 (2%) | |POLY-3 RATE (b) | 0/30.88 0/36.61 2/42.60 1/32.52 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.7% 3.1% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 588 530 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.189 (e) P=0.329 P=0.525 | |POLY 3 | P=0.205 (e) P=0.314 P=0.510 | |POLY 1.5 | P=0.219 (e) P=0.290 P=0.513 | |POLY 6 | P=0.174 (e) P=0.342 P=0.496 | |LOGISTIC REGRESSION| P=0.225 (e) P=0.278 P=0.503 | |COCH-ARM / FISHERS | P=0.225 (e) P=0.257 P=0.510 | |ORDER RESTRICTED | P=0.236 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 46 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland | | Cytoplasmic Alteration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/51 (0%) 3/53 (6%) 1/53 (2%) 0/53 (0%) | |POLY-3 RATE (b) | 0/30.88 3/36.91 1/42.13 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 8.1% 2.4% 0.0% | |TERMINAL (d) | 0/15 (0%) 2/16 (13%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 645 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.519N P=0.145 P=0.585 (e) | |POLY 3 | P=0.361N P=0.152 P=0.561 (e) | |POLY 1.5 | P=0.367N P=0.142 P=0.543 (e) | |POLY 6 | P=0.368N P=0.161 P=0.579 (e) | |LOGISTIC REGRESSION| P=0.433N P=0.159 P=0.585 (e) | |COCH-ARM / FISHERS | P=0.395N P=0.129 P=0.510 (e) | |ORDER RESTRICTED | P=0.250N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 18/51 (35%) 21/53 (40%) 26/53 (49%) 17/53 (32%) | |POLY-3 RATE (b) | 18/36.64 21/40.94 26/43.52 17/36.71 | |POLY-3 PERCENT (g) | 49.1% 51.3% 59.7% 46.3% | |TERMINAL (d) | 4/15 (27%) 7/16 (44%) 18/23 (78%) 3/7 (43%) | |FIRST INCIDENCE | 400 541 637 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.225 P=0.532N P=0.469N P=0.396 | |POLY 3 | P=0.501N P=0.515 P=0.224 P=0.497N | |POLY 1.5 | P=0.435N P=0.483 P=0.200 P=0.445N | |POLY 6 | P=0.425 P=0.531 P=0.219 P=0.582 | |LOGISTIC REGRESSION| P=0.406N P=0.538 P=0.434 P=0.425N | |COCH-ARM / FISHERS | P=0.429N P=0.400 P=0.111 P=0.444N | |ORDER RESTRICTED | P=0.413N (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 47 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 39/52 (75%) 41/53 (77%) 42/52 (81%) 37/52 (71%) | |POLY-3 RATE (b) | 39/47.51 41/47.65 42/47.95 37/44.38 | |POLY-3 PERCENT (g) | 82.1% 86.1% 87.6% 83.4% | |TERMINAL (d) | 8/15 (53%) 15/16 (94%) 22/23 (96%) 6/7 (86%) | |FIRST INCIDENCE | 126 40 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.248 P=0.353N P=0.056N P=0.344 | |POLY 3 | P=0.477 P=0.395 P=0.313 P=0.550 | |POLY 1.5 | P=0.480N P=0.472 P=0.337 P=0.534N | |POLY 6 | P=0.256 P=0.258 P=0.260 P=0.327 | |LOGISTIC REGRESSION| P=0.338N P=0.514 P=0.491 P=0.404N | |COCH-ARM / FISHERS | P=0.363N P=0.478 P=0.319 P=0.413N | |ORDER RESTRICTED | P=0.470 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/53 (2%) 1/52 (2%) 3/52 (6%) | |POLY-3 RATE (b) | 0/31.36 1/36.86 1/41.53 3/32.34 | |POLY-3 PERCENT (g) | 0.0% 2.7% 2.4% 9.3% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- 659 727 (T) 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.034 * P=0.548 P=0.585 P=0.146 | |POLY 3 | P=0.054 P=0.532 P=0.555 P=0.121 | |POLY 1.5 | P=0.054 P=0.521 P=0.536 P=0.123 | |POLY 6 | P=0.052 P=0.543 P=0.576 P=0.112 | |LOGISTIC REGRESSION| P=0.048 * P=0.526 P=0.585 P=0.121 | |COCH-ARM / FISHERS | P=0.052 P=0.505 P=0.500 P=0.121 | |ORDER RESTRICTED | P=0.038 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 48 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 49/52 (94%) 52/53 (98%) 52/52 (100%) 50/52 (96%) | |POLY-3 RATE (b) | 49/49.42 52/52.75 52/52.00 50/50.58 | |POLY-3 PERCENT (g) | 99.2% 98.6% 100.0% 98.9% | |TERMINAL (d) | 15/15 (100%) 16/16 (100%) 23/23 (100%) 7/7 (100%) | |FIRST INCIDENCE | 126 40 185 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.127 P=0.338N P=0.023N* P=0.149 | |POLY 3 | P=0.725 P=0.807N P=0.958 P=0.895N | |POLY 1.5 | P=0.548 P=0.779 P=0.503 P=0.787 | |POLY 6 | P=0.782N P=0.845N P=1.000 P=0.985N | |LOGISTIC REGRESSION| P=0.435 P=0.347 P=0.303 P=0.541 | |COCH-ARM / FISHERS | P=0.391 P=0.302 P=0.121 P=0.500 | |ORDER RESTRICTED | P=0.540 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 5/53 (9%) 3/52 (6%) 6/52 (12%) | |POLY-3 RATE (b) | 0/31.36 5/39.29 3/42.88 6/33.93 | |POLY-3 PERCENT (g) | 0.0% 12.7% 7.0% 17.7% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 163 440 531 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.030 * P=0.056 P=0.210 P=0.028 * | |POLY 3 | P=0.041 * P=0.053 P=0.185 P=0.018 * | |POLY 1.5 | P=0.037 * P=0.045 * P=0.159 P=0.017 * | |POLY 6 | P=0.042 * P=0.064 P=0.218 P=0.016 * | |LOGISTIC REGRESSION| P=0.031 * P=0.026 * P=0.088 P=0.018 * | |COCH-ARM / FISHERS | P=0.031 * P=0.030 * P=0.121 P=0.013 * | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 49 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Spleen: Red Pulp | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 1/53 (2%) 0/52 (0%) 2/52 (4%) | |POLY-3 RATE (b) | 0/31.36 1/36.99 0/41.53 2/32.44 | |POLY-3 PERCENT (g) | 0.0% 2.7% 0.0% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 618 --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.134 P=0.559 (e) P=0.260 | |POLY 3 | P=0.148 P=0.533 (e) P=0.243 | |POLY 1.5 | P=0.145 P=0.522 (e) P=0.244 | |POLY 6 | P=0.148 P=0.544 (e) P=0.230 | |LOGISTIC REGRESSION| P=0.137 P=0.511 (e) P=0.227 | |COCH-ARM / FISHERS | P=0.136 P=0.505 (e) P=0.248 | |ORDER RESTRICTED | P=0.078 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperkeratosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 3/53 (6%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 0/31.36 3/37.14 1/41.62 2/32.22 | |POLY-3 PERCENT (g) | 0.0% 8.1% 2.4% 6.2% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 618 678 681 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.229 P=0.162 P=0.627 P=0.192 | |POLY 3 | P=0.333 P=0.150 P=0.555 P=0.241 | |POLY 1.5 | P=0.329 P=0.139 P=0.535 P=0.245 | |POLY 6 | P=0.325 P=0.163 P=0.577 P=0.226 | |LOGISTIC REGRESSION| P=0.289 P=0.150 P=0.553 P=0.207 | |COCH-ARM / FISHERS | P=0.309 P=0.125 P=0.495 P=0.252 | |ORDER RESTRICTED | P=0.190 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 50 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 5/53 (9%) 6/51 (12%) 8/53 (15%) | |POLY-3 RATE (b) | 3/32.29 5/38.68 6/42.62 8/34.42 | |POLY-3 PERCENT (g) | 9.3% 12.9% 14.1% 23.2% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 2/23 (9%) 1/7 (14%) | |FIRST INCIDENCE | 391 301 320 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.026 * P=0.440 P=0.484 P=0.046 * | |POLY 3 | P=0.077 P=0.458 P=0.395 P=0.109 | |POLY 1.5 | P=0.079 P=0.423 P=0.336 P=0.113 | |POLY 6 | P=0.068 P=0.496 P=0.462 P=0.093 | |LOGISTIC REGRESSION| P=0.073 P=0.362 P=0.257 P=0.109 | |COCH-ARM / FISHERS | P=0.073 P=0.369 P=0.234 P=0.107 | |ORDER RESTRICTED | P=0.094 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/52 (2%) 0/53 (0%) 1/51 (2%) 2/53 (4%) | |POLY-3 RATE (b) | 1/32.34 0/36.61 1/41.94 2/33.34 | |POLY-3 PERCENT (g) | 3.1% 0.0% 2.4% 6.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 201 --- 573 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.273 P=0.496N P=0.719N P=0.524 | |POLY 3 | P=0.255 P=0.475N P=0.699N P=0.511 | |POLY 1.5 | P=0.261 P=0.484N P=0.724N P=0.515 | |POLY 6 | P=0.243 P=0.467N P=0.670N P=0.489 | |LOGISTIC REGRESSION| P=0.234 P=0.484N P=0.567 P=0.476 | |COCH-ARM / FISHERS | P=0.259 P=0.495N P=0.748 P=0.507 | |ORDER RESTRICTED | P=0.224 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 51 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/52 (6%) 3/53 (6%) 2/51 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 3/32.17 3/37.14 2/42.54 2/32.69 | |POLY-3 PERCENT (g) | 9.3% 8.1% 4.7% 6.1% | |TERMINAL (d) | 1/15 (7%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | 574 618 320 603 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.407N P=0.578N P=0.338N P=0.568N | |POLY 3 | P=0.337N P=0.596N P=0.376N P=0.493N | |POLY 1.5 | P=0.341N P=0.617N P=0.419N P=0.485N | |POLY 6 | P=0.338N P=0.577N P=0.334N P=0.528N | |LOGISTIC REGRESSION| P=0.354N P=0.599N P=0.567N P=0.490N | |COCH-ARM / FISHERS | P=0.358N P=0.652N P=0.509N P=0.491N | |ORDER RESTRICTED | P=0.433N (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 37/50 (74%) 36/41 (88%) 47/49 (96%) 41/44 (93%) | |POLY-3 RATE (b) | 37/45.02 36/36.59 47/48.09 41/41.71 | |POLY-3 PERCENT (g) | 82.2% 98.4% 97.7% 98.3% | |TERMINAL (d) | 9/15 (60%) 14/14 (100%) 22/23 (96%) 7/7 (100%) | |FIRST INCIDENCE | 126 531 185 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.029 * P=0.293N P=0.233N P=0.115 | |POLY 3 | P<0.001 ** P=0.014 * P=0.010 * P=0.010 * | |POLY 1.5 | P<0.001 ** P=0.018 * P=0.005 ** P=0.008 ** | |POLY 6 | P=0.002 ** P=0.013 * P=0.017 * P=0.012 * | |LOGISTIC REGRESSION| P=0.005 ** P=0.168 P=0.009 ** P=0.016 * | |COCH-ARM / FISHERS | P=0.003 ** P=0.082 P=0.002 ** P=0.012 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 52 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: C-Cell | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 18/52 (35%) 16/50 (32%) 19/48 (40%) | |POLY-3 RATE (b) | 12/33.93 18/39.59 16/42.33 19/35.88 | |POLY-3 PERCENT (g) | 35.4% 45.5% 37.8% 53.0% | |TERMINAL (d) | 5/15 (33%) 6/16 (38%) 12/23 (52%) 2/7 (29%) | |FIRST INCIDENCE | 541 531 554 484 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.023 * P=0.321 P=0.412N P=0.036 * | |POLY 3 | P=0.122 P=0.255 P=0.508 P=0.096 | |POLY 1.5 | P=0.100 P=0.201 P=0.401 P=0.078 | |POLY 6 | P=0.133 P=0.320 P=0.586N P=0.108 | |LOGISTIC REGRESSION| P=0.078 P=0.229 P=0.591N P=0.066 | |COCH-ARM / FISHERS | P=0.065 P=0.140 P=0.216 P=0.058 | |ORDER RESTRICTED | P=0.106 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Thyroid Gland: Follicular Cell | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/52 (17%) 28/52 (54%) 26/50 (52%) 16/48 (33%) | |POLY-3 RATE (b) | 9/37.19 28/42.67 26/45.46 16/37.59 | |POLY-3 PERCENT (g) | 24.2% 65.6% 57.2% 42.6% | |TERMINAL (d) | 2/15 (13%) 12/16 (75%) 15/23 (65%) 2/7 (29%) | |FIRST INCIDENCE | 201 247 320 72 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.059 P=0.002 ** P=0.030 * P=0.053 | |POLY 3 | P=0.229 P<0.001 ** P<0.001 ** P=0.066 | |POLY 1.5 | P=0.198 P<0.001 ** P<0.001 ** P=0.064 | |POLY 6 | P=0.236 P<0.001 ** P=0.005 ** P=0.060 | |LOGISTIC REGRESSION| P=0.122 P<0.001 ** P<0.001 ** P=0.025 * | |COCH-ARM / FISHERS | P=0.130 P<0.001 ** P<0.001 ** P=0.053 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 53 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/12 (83%) 10/10 (100%) 8/9 (89%) 18/19 (95%) | |POLY-3 RATE (b) | 10/12.00 10/10.00 8/9.00 18/18.62 | |POLY-3 PERCENT (g) | 83.3% 100.0% 88.9% 96.7% | |TERMINAL (d) | 5/7 (71%) 4/4 (100%) 5/6 (83%) 4/4 (100%) | |FIRST INCIDENCE | 405 531 573 188 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.480 P=0.285N P=0.011 * | |POLY 3 | P=0.225 P=0.272 P=0.602 P=0.258 | |POLY 1.5 | P=0.263 P=0.272 P=0.602 P=0.294 | |POLY 6 | P=0.175 P=0.272 P=0.602 P=0.208 | |LOGISTIC REGRESSION| P=0.412 (e) (e) P=0.450 | |COCH-ARM / FISHERS | P=0.311 P=0.286 P=0.612 P=0.328 | |ORDER RESTRICTED | P=0.100 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Tooth: Peridontal Tissue | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/12 (17%) 0/10 (0%) 1/9 (11%) 0/19 (0%) | |POLY-3 RATE (b) | 2/9.81 0/8.18 1/8.19 0/12.13 | |POLY-3 PERCENT (g) | 20.4% 0.0% 12.2% 0.0% | |TERMINAL (d) | 2/7 (29%) 0/4 (0%) 1/6 (17%) 0/4 (0%) | |FIRST INCIDENCE | 727 (T) --- 727 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.229N P=0.362N P=0.558N P=0.362N | |POLY 3 | P=0.126N P=0.268N P=0.566N P=0.174N | |POLY 1.5 | P=0.120N P=0.267N P=0.579N P=0.158N | |POLY 6 | P=0.141N P=0.277N P=0.553N P=0.202N | |LOGISTIC REGRESSION| P=0.229N (e) P=0.558N (e) | |COCH-ARM / FISHERS | P=0.106N P=0.286N P=0.612N P=0.142N | |ORDER RESTRICTED | P=0.041N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 54 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 2/2.75 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 72.8% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.042 * (e) (e) P=0.245 | |POLY 3 | (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=1.000N (e) (e) P=1.000 | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 2/3 (67%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 2/2.08 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 96.3% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 588 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.164 (e) (e) P=0.471 | |POLY 3 | (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=1.000N (e) (e) P=1.000 | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 55 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Ureter: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 3/3 (100%) | |POLY-3 RATE (b) | 0/0.00 0/0.00 0/0.00 3/3.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% | |TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | --- --- --- 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Urinary Bladder | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/51 (8%) 7/52 (13%) 4/52 (8%) 6/53 (11%) | |POLY-3 RATE (b) | 4/32.86 7/39.11 4/42.47 6/34.02 | |POLY-3 PERCENT (g) | 12.2% 17.9% 9.4% 17.6% | |TERMINAL (d) | 0/15 (0%) 2/16 (13%) 1/23 (4%) 1/7 (14%) | |FIRST INCIDENCE | 391 301 573 309 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.338 P=0.358 P=0.421N P=0.276 | |POLY 3 | P=0.443 P=0.366 P=0.497N P=0.387 | |POLY 1.5 | P=0.452 P=0.331 P=0.543N P=0.402 | |POLY 6 | P=0.417 P=0.398 P=0.448N P=0.337 | |LOGISTIC REGRESSION| P=0.429 P=0.247 P=0.639 P=0.395 | |COCH-ARM / FISHERS | P=0.435 P=0.274 P=0.631N P=0.395 | |ORDER RESTRICTED | P=0.427 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 56 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Urinary Bladder: Transitional Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/51 (2%) 1/52 (2%) 2/52 (4%) 2/53 (4%) | |POLY-3 RATE (b) | 1/31.35 1/36.79 2/41.91 2/32.25 | |POLY-3 PERCENT (g) | 3.2% 2.7% 4.8% 6.2% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | 574 301 618 660 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.265 P=0.734N P=0.642 P=0.425 | |POLY 3 | P=0.322 P=0.725N P=0.599 P=0.510 | |POLY 1.5 | P=0.335 P=0.736N P=0.568 P=0.518 | |POLY 6 | P=0.296 P=0.716N P=0.631 P=0.481 | |LOGISTIC REGRESSION| P=0.337 P=0.741 P=0.540 P=0.510 | |COCH-ARM / FISHERS | P=0.338 P=0.748N P=0.507 P=0.515 | |ORDER RESTRICTED | P=0.428 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Adenomyosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 0/53 (0%) 2/52 (4%) 0/53 (0%) | |POLY-3 RATE (b) | 0/31.36 0/36.61 2/41.91 0/31.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.8% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/16 (0%) 1/23 (4%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 618 --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.489 (e) P=0.344 (e) | |POLY 3 | P=0.491 (e) P=0.307 (e) | |POLY 1.5 | P=0.521 (e) P=0.281 (e) | |POLY 6 | P=0.419 (e) P=0.338 (e) | |LOGISTIC REGRESSION| P=0.541 (e) P=0.286 (e) | |COCH-ARM / FISHERS | P=0.541 (e) P=0.248 (e) | |ORDER RESTRICTED | P=0.305 (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 57 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/52 (0%) 2/53 (4%) 1/52 (2%) 1/53 (2%) | |POLY-3 RATE (b) | 0/31.36 2/36.91 1/42.13 1/32.01 | |POLY-3 PERCENT (g) | 0.0% 5.4% 2.4% 3.1% | |TERMINAL (d) | 0/15 (0%) 1/16 (6%) 0/23 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- 645 535 700 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.393 P=0.275 P=0.552 P=0.413 | |POLY 3 | P=0.474 P=0.274 P=0.558 P=0.504 | |POLY 1.5 | P=0.476 P=0.261 P=0.537 P=0.507 | |POLY 6 | P=0.454 P=0.288 P=0.580 P=0.490 | |LOGISTIC REGRESSION| P=0.464 P=0.278 P=0.442 P=0.456 | |COCH-ARM / FISHERS | P=0.463 P=0.252 P=0.500 P=0.505 | |ORDER RESTRICTED | P=0.329 (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/52 (23%) 10/53 (19%) 6/52 (12%) 4/53 (8%) | |POLY-3 RATE (b) | 12/35.65 10/39.29 6/42.51 4/33.98 | |POLY-3 PERCENT (g) | 33.7% 25.5% 14.1% 11.8% | |TERMINAL (d) | 2/15 (13%) 3/16 (19%) 4/23 (17%) 0/7 (0%) | |FIRST INCIDENCE | 391 331 535 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.025N* P=0.264N P=0.018N* P=0.065N | |POLY 3 | P=0.010N* P=0.296N P=0.035N* P=0.025N* | |POLY 1.5 | P=0.009N** P=0.319N P=0.049N* P=0.021N* | |POLY 6 | P=0.012N* P=0.298N P=0.027N* P=0.042N* | |LOGISTIC REGRESSION| P=0.011N* P=0.344N P=0.064N P=0.025N* | |COCH-ARM / FISHERS | P=0.012N* P=0.386N P=0.097N P=0.025N* | |ORDER RESTRICTED | P=0.018N* (e) (e) (e) | |=================================================================================================================================| Date: 10/01/03 EXPERIMENT: 96007 TEST: 01 Page 58 Statistical Analysis of Non-neoplastic Lesions in Rats(SPRAGUE-DAWLEY) - TOXIC EQUIVALENCY FACTOR EVALUATION ( Terminal Sacrifice at 104 weeks |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 26/52 (50%) 29/53 (55%) 27/52 (52%) 11/53 (21%) | |POLY-3 RATE (b) | 26/41.07 29/45.96 27/46.70 11/35.60 | |POLY-3 PERCENT (g) | 63.3% 63.1% 57.8% 30.9% | |TERMINAL (d) | 7/15 (47%) 8/16 (50%) 12/23 (52%) 2/7 (29%) | |FIRST INCIDENCE | 321 247 440 555 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.016N* P=0.476N P=0.098N P=0.023N* | |POLY 3 | P=0.002N** P=0.583N P=0.377N P=0.002N** | |POLY 1.5 | P<0.001N** P=0.545 P=0.449N P<0.001N** | |POLY 6 | P=0.011N* P=0.582N P=0.329N P=0.010N* | |LOGISTIC REGRESSION| P<0.001N** P=0.433 P=0.490N P<0.001N** | |COCH-ARM / FISHERS | P<0.001N** P=0.387 P=0.500 P=0.002N** | |ORDER RESTRICTED | P=0.002N** (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 NG/KG 300 550 1000 | | | NG/KG NG/KG NG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 23/52 (44%) 26/53 (49%) 32/52 (62%) 9/53 (17%) | |POLY-3 RATE (b) | 23/35.31 26/41.15 32/45.02 9/34.37 | |POLY-3 PERCENT (g) | 65.1% 63.2% 71.1% 26.2% | |TERMINAL (d) | 12/15 (80%) 12/16 (75%) 21/23 (91%) 3/7 (43%) | |FIRST INCIDENCE | 496 403 327 244 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.063N P=0.537N P=0.369N P=0.065N | |POLY 3 | P<0.001N** P=0.527N P=0.361 P<0.001N** | |POLY 1.5 | P<0.001N** P=0.560 P=0.213 P<0.001N** | |POLY 6 | P=0.002N** P=0.434N P=0.543 P<0.001N** | |LOGISTIC REGRESSION| P<0.001N** P=0.504N P=0.493 P<0.001N** | |COCH-ARM / FISHERS | P=0.003N** P=0.382 P=0.058 P=0.002N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).